Tumor-Selective Biodegradation-Regulated Photothermal H2 S Donor for Redox Dyshomeostasis- and Glycolysis
Yi Wang1, Min Qian2, Yilin Du2
1Center for Advanced Low-dimension Materials, State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201600, China.
Abstract:
H2 S-mediated tumor therapy has received great attention due to its unique physiological activity and synergistical enhancement, but suffers from limited H2 S donors with promised biosafety to regulate the H2 S delivery and subsequently the elusive pathway to augment the combined therapy. Herein, a PEGylated porous molybdenum disulfide nanoflower (MSP) with abundant defects is facilely synthesized for tumor-targeted theranostics. MSP possesses good water-dispersity and high photothermal ability, which is used for photoacoustic imaging and photothermal therapy. Interestingly, MSP is selectively degraded upon exposure to superfluous glutathione (GSH) within tumor cells, the mechanism of which is investigated, as a reduction-coordination reaction. This special degradation induces redox dyshomeostasis via GSH depletion for reactive oxygen species-accumulated chemodynamic therapy. Meanwhile, the selective biodegradation of MSP regulates a sustained H2 S release within tumor and achieves a targeted H2 S gas therapy via enhancing the glycolysis to acidify the tumor cells (glycolysis disorder). Synergistically, these performances are further enhanced via near-infrared photothermal heating, where excellent therapeutic outcomes with good biosafety are accomplished in vitro and in vivo. These characteristics, together with the unique biodegradation and no obvious side-effects of the nanoparticles, suggest a potential therapeutic strategy for precise tumor treatments.
Insights
This study introduces a novel molybdenum disulfide nanoflower (MSP) for enhanced cancer therapy. MSP enables targeted drug delivery, photothermal therapy, and hydrogen sulfide (H₂S) gas release, improving treatment outcomes with good biosafety.
Area of Science:
- Biomedical Engineering
- Materials Science
- Oncology
Background:
- Hydrogen sulfide (H₂S)-mediated tumor therapy shows promise but is limited by safe and effective H₂S delivery methods.
- Developing novel nanomaterials for targeted cancer theranostics remains a critical challenge.
Purpose of the Study:
- To synthesize and characterize a PEGylated porous molybdenum disulfide nanoflower (MSP) for tumor-targeted theranostics.
- To investigate the mechanism of MSP degradation and its application in combined cancer therapy.
- To evaluate the synergistic therapeutic effects of MSP-mediated chemodynamic therapy, H₂S gas therapy, and photothermal therapy.
Main Methods:
- Facile synthesis of PEGylated porous molybdenum disulfide nanoflower (MSP).
- Investigation of MSP degradation mechanism triggered by glutathione (GSH).
- In vitro and in vivo evaluation of combined theranostic applications including photoacoustic imaging, photothermal therapy, chemodynamic therapy, and H₂S gas therapy.
Main Results:
- MSP demonstrated good water-dispersity and high photothermal conversion efficiency.
- Selective degradation of MSP in tumor cells induced redox dyshomeostasis and GSH depletion, facilitating chemodynamic therapy.
- Biodegradation of MSP led to sustained H₂S release, enhancing glycolysis and tumor cell acidification for H₂S gas therapy.
- Synergistic treatment combining photothermal heating, chemodynamic therapy, and H₂S gas therapy achieved excellent therapeutic outcomes with good biosafety in vitro and in vivo.
Conclusions:
- The developed MSP serves as a multifunctional theranostic platform for precise tumor treatment.
- The unique biodegradation mechanism enables targeted H₂S delivery and synergistic therapeutic effects.
- This strategy offers a promising approach for advanced cancer therapy with minimal side effects.
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